Permanent cures for inflammatory bowel disease (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), are lacking. In Sweden, 1400 new patients are diagnosed with IBD each year, with the peak incidence at 20 years of age, resulting in life long treatment with cortisone and/or immunosuppressive drugs with severe side effects. Furthermore, IBD often results in surgical bowel resection and permanent stoma, which is a major handicap. Ulcerative colitis also increases the risk of cancer in the large bowel.
IBD is thought to be an autoimmune disease due to abnormalities in the immunological response to normally harmless mucosal antigens. Based on the cytokines involved the inflammation of CD is characterized as a TH1 cell mediated immune response. UC is proposed to have a TH2 cell mediated response, though this has not been clearly shown (Fuss I J et al., 1996. J. Immunol. 157:1261-70; Mullin G E et al., 1996. Inflamm. Bowel Dis. 2:16-26).
Cytokines act as regulators of immunological responses as they stimulate differentiation and proliferation of the cellular elements involved. CD4+ helper T cells may differentiate into two major subpopulations of effector cells, TH1 cells when stimulated by IL-12 and TH2 cells when stimulated by IL-4. TH1 cells secrete IFN-γ that stimulates phagocyte- and cytolytic T cell dependent reactions against intracellular microbes such as viruses or intracellular bacteria. TH2 cells secrete IL-4 and IL-5 that stimulate production of IgE and eosinophil/mast cell mediated defense against parasites. TH2 also functions to down regulate TH1 responses.